ProjectSummary AutosomalDominantPolycystickidneydisease(ADPKD)ischaracterizedbynumerouscysts withinthekidneysofafflictedindividuals.ThecystsformedinADPKDcangreatlyenlargethe kidneyswhilereplacingthenormalkidneystructures,resultinginreducedkidneyfunctionand progressiontoend-stagerenaldisease,thatcanonlybetreatedbylifelongdialysisorkidney transplants.Asadiseasethataffects1in800~1000individuals,ADPKDisamongthemost commongeneticdisorders.IntheUnitedStates,thereare600,000individuals,andworldwide 12.5million,withPKD[1].Thus,ADPKDrepresentsamajorpublichealthissue,and accountsforhundredsofmillions(andperhapsoverabillion)ofdollarsinhealthcarecosts, particularlyfordialysistreatmentsandthecostofdrugsthatpreventtransplantrejections,as wellasthecostinvolvedofdecreasedproductivityandimpairedqualityoflifeofindividuals withADPKD.Forallthesereasons,itisofgreatimportancetodiscovertreatmentsthat directlyaffectthemolecularcausesofADPKD,andthatwillpreventtheprogressiontoend- stagerenaldiseaseanddialysisortransplantation. Overthepast5yearstheKreidberglaboratoryhasinvestigatedtheroleofWntsignalingin thepathogenesisofADPKD.Dr.Kreidberg?slaboratoryhasfoundthatWntsignalingand?- cateninexpressionishighlyelevatedincystliningcellsinADPKD.Inthisgranttheypropose toextendtheirstudiestounderstandhowaputative?-catenintargetgene,fibronectin,affects cystformation.Fibronectinisakeyextracellularmatrixgeneprimarilyfoundina mesenchymalmatrix,butover-expressedincystickidneys.Wewillstudytheroleof integrin:fibronectininteractionsinADPKD.